• Division of Cancer Prevention, National Cancer Institute, Bethesda, MD. Electronic address: pp4f@nih.gov.
• Department of Radiology, National Jewish Health, Denver, CO.
• Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO.

BACKGROUND: Incidental respiratory-disease related findings are frequently observed on low-dose CT (LDCT) lung cancer screenings. We analyzed data from the National Lung Screening Trial (NLST) to assess the relationship between such findings and respiratory disease mortality (RDM), excluding lung cancer.

RESEARCH QUESTION: Are incidental respiratory findings on LDCT associated with increased RDM?

STUDY DESIGN AND METHODS: NLST LDCT arm subjects received three annual screens. Trial radiologists noted findings related to possible lung cancer, as well as respiratory-related incidental findings. Demographics, smoking history and medical history were captured in a baseline questionnaire. Kaplan-Meier curves were used to assess cumulative RDM. Multivariate proportional hazards models were used to assess risk factors for RDM; in addition to incidental CT findings, variables included respiratory disease history (COPD/emphysema, asthma), smoking history, and demographic factors (age, race, sex, BMI).

RESULTS: Of 26,722 NLST LDCT arm subjects, 25,002 received the baseline and a subsequent LDCT screen. 59% were men and 26.5% were age 65+ at baseline; 10.6% reported a history of COPD/emphysema. Emphysema on LDCT was reported in 30.7% of subjects at baseline and in 44.2% at any screen. Of those with emphysema on baseline LDCT, 18% reported a history of COPD/emphysema. Median mortality follow-up was 10.3 years. There were 3639 deaths; 934 were from respiratory diseases. Among subjects without a history of COPD/emphysema, 10-year cumulative RDM was 3.8% for subjects with versus 1.5% for subjects without emphysema on CT; corresponding rates among subjects with a COPD/emphysema history were 15.2% versus 7.2%. Emphysema on LDCT was associated with a significantly elevated RDM HR (2.27, 95% CI:1.92-2.7) in the multivariate model. Reticular opacities (including honeycombing/fibrosis/scar) also had a significantly elevated HR (1.39, 95% CI: 1.19-1.62).

INTERPRETATION: Incidental respiratory disease-related findings observed on NLST LDCT screens were frequent and associated with increased mortality from respiratory diseases.